Peritoneal Dissemination Of Colon Cancer Research Articles

Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination.

Intraperitoneal administration of anticancer nanoparticles is a rational strategy for preventing peritoneal dissemination of colon cancer due to the prolonged retention of nanoparticles in the abdominal cavity. However, instability of nanoparticles in body fluids causes inefficient retention, reducing its anticancer effects. We have previously developed anticancer nanoparticles containing tocopheryl succinate, which showed high in vivo stability and multifunctional anticancer effects. In the present study, we have demonstrated that peritoneal dissemination derived from colon cancer was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. The biodistribution of tocopheryl succinate nanoparticles was evaluated using inductively coupled plasma mass spectroscopy and imaging analysis in mice administered quantum dot encapsulated tocopheryl succinate nanoparticles. Intraperitoneal administration of tocopheryl succinate nanoparticles showed longer retention in the abdominal cavity than by its intravenous (i.v.) administration. Moreover, due to effective biodistribution, tumor growth was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. Furthermore, the anticancer effect was attributed to the inhibition of cancer cell proliferation and improvement of the intraperitoneal microenvironment, such as decrease in the levels of vascular endothelial growth factor A, interleukin 10, and M2‐like phenotype of tumor‐associated macrophages. Collectively, intraperitoneal administration of tocopheryl succinate nanoparticles is expected to have multifaceted antitumor effects against colon cancer with peritoneal dissemination.

STING activation normalizes the intraperitoneal vascular-immune microenvironment and suppresses peritoneal carcinomatosis of colon cancer

BackgroundPeritoneal carcinomatosis is a fatal clinical presentation of colon cancer, characterized by unresponsiveness to conventional anticancer therapies, including immune checkpoint inhibitors. Here, we elucidated the immune-evasion mechanisms during the peritoneal...

Oncolytic vaccinia virus reinvigorates peritoneal immunity and cooperates with immune checkpoint inhibitor to suppress peritoneal carcinomatosis in colon cancer

BackgroundPeritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by...

Potential Usefulness of Three-dimensional Navigation Tools for the Resection of Intra-abdominal Recurrence of Colorectal Cancer

PurposeComplete resection of intra-abdominal recurrence of colorectal cancer is difficult because of complex anatomical changes following primary surgery and indefinite cancer demarcation. Here, we demonstrate the effect of surgery using three-dimensional (3D) printed model and 3D virtual images on the achievement of complete resection. MethodsWe enrolled 11 cases who had undergone combined resection of adjacent organs for colorectal cancer recurrence, including localized peritoneal dissemination of colon cancer and local recurrence of rectal cancer, between January 2016 and July 2018. We created 3D virtual images of nine cases and 3D models of two cases and used them for intraoperative navigation. ResultsSimulation and navigation using 3D technologies potentially helped the surgeons to comprehend the complex anatomy and perform challenging surgeries. Macroscopic negative margins were achieved in all cases, including R0 resection in 8 of the 11 cases. Conclusion3D navigation tools are potentially useful to complete the resection of intra-abdominal recurrence of colorectal cancer.

Complete remission of peritoneal dissemination of colon cancer by alternate-day S-1 and oxaliplatin plus bevacizumab treatment and maintenance chemotherapy comprising alternate-day S-1 plus bevacizumab: A case report.

A 56-year-old man diagnosed with sigmoid colon cancer underwent sigmoid colectomy. Nine months later, his serum carcinoembryonic antigen (CEA) level had increased, and the diagnosis of recurrent peritoneal dissemination was made based on positron emission tomography/computed tomography (PET/CT) findings. Although systemic chemotherapy comprising S-1 and oxaliplatin (SOX) plus bevacizumab was initiated, severe diarrhea occurred on day 4 of the second cycle despite reduction in S-1 dose. By changing the daily oral intake schedule for S-1 to an alternate-day intake from the third cycle (modified SOX plus bevacizumab), the patient was able to continue undergoing chemotherapy without any adverse gastrointestinal effects. All tumors disappeared after four cycles, and the patients received eight cycles of modified SOX plus bevacizumab followed by maintenance chemotherapy comprising alternate-day S-1 plus bevacizumab. Maintenance chemotherapy was discontinued after 17 cycles owing to adverse events, including thrombocytopenia, corneal and lacrimal duct disorders, and hyperbilirubinemia. The patient has been radiographically confirmed to be in remission for 5 years without any recurrence, and his serum CEA level has been within normal range for >3 years. To conclude, compared with the conventional consecutive treatment, alternate-day SOX plus bevacizumab treatment may reduce the adverse effects of these chemotherapeutic drugs.

Inhibition of peritoneal dissemination of colon cancer by hyperthermic CO2 insufflation: A novel approach to prevent intraperitoneal tumor spread.

BackgroundThe increasing use of laparoscopic surgery for advanced gastrointestinal cancer raises concerns about intra-peritoneal tumor spread. Prevention of peritoneal dissemination is extremely important but a preventive modality is lacking. The aim of this study was to examine a novel approach (hyperthermic CO2 insufflation, HT-CO2) for preventing peritoneal dissemination during laparoscopic surgery.MethodsA peritoneal dissemination model was established in Balb/c nu/nu mice by intraperitoneal injection of human colon cancer cells (SW1116, 1×106). The mice (n = 48) were subsequently randomized into two groups and subjected to hyperthermic CO2 (43°C, >95% humidity, HT-CO2 group) or standard normothermic CO2 (21°C, <1% relative humidity, NT-CO2 group) insufflation for 3 hours. The mice were sacrificed 28 days later. The peritoneal dissemination was quantitatively analyzed by counting and weighing the peritoneal nodules. The port sites and ascites volume were measured. The peritoneal damage of HT-CO2 was histologically examined with light microscopy and scanning electron microscopy. Intra-abdominal adhesions were evaluated 4 weeks later.ResultsThe number of peritoneal nodules in the HT-CO2 group was significantly less than that in the NT-CO2 group (10.21±3.72 vs. 67.12±5.49, P<0.01). The mean weight of metastatic tumors in the HT-CO2 group was significantly lower than that in the NT-CO2 group (0.31±0.10g vs. 2.16±0.31g, P<0.01). Massive ascites were found in the NT-CO2 group while significantly less ascites developed in HT-CO2- treated mice (8.26±0.31ml vs. 1.27±0.28ml, P<0.01). No port-site metastases were detected in the HT-CO2 group while the incidence of the NT-CO2 group was 12.5% (3/24). HT-CO2 subjection resulted in slight peritoneal damage; the peritoneum returned to normal within five days. No adhesions formed after HT-CO2 treatment.ConclusionsHT-CO2 can suppress peritoneal dissemination of colon cancer cells and only causes slight and transient peritoneal damage. HT-CO2 may serve as a promising adjuvant treatment for preventing peritoneal dissemination in laparoscopic resection of advanced colorectal cancer.

Preparation of anti-tumor nanoparticle and its inhibition to peritoneal dissemination of colon cancer.

Background5-Fluorouracil (5-FU) is one of the most classic chemotherapy drugs. Nanoparticle drug delivery vehicles offer superiority over target effect enhancement and abatement of side effects. Little is known however as to the specific effect of nanoparticle on peritoneal dissemination of colon cancer. The aim of this study is to prepare one NPs (nanoparticles) loaded with 5-FU and investigate the characteristic of NPs and the role of it in peritoneal metastasis nodules formation of human colon cancer.Methodology/Principal FindingsPrepared the NPs (nanoparticles) loaded with 5-FU (5-Fluorouracil) by PEG-PLGA with the method of double emulsion. Then evaluate the characteristics of the NPs by scanning electron microscopy, analyzing the particle diameter distribution and determining the loading efficiency. Detect the release features of NPs in vitro and in vivo. Nude mice with peritoneal metastases were treated with 5-FU solution or 5-FU-NPs through peritoneal cavity. Count the nodules on peritoneum and mesenterium and survey the size of them. We got NPs with average-diameter of 310 nm. In vitro release test shows NPs can release equably for 5 days with release rate of 99.2%. In vivo, NPs group can keep higher plasma concentration of 5-FU longer than it in solution group. The number of peritoneal dissemination nodule below 1 mm in 5-FU-sol group(17.3±3.5) and 5-FU-NP group(15.2±3.2) is less than control group(27.2±4.7)(P<0.05). The total number of nodules in 5-FU-NP group(28.7±4.2) is significantly smaller than in 5-FU-sol group(37.7±6.3) (P<0.05).Conclusions/SignificanceThe novel anti-tumor nanoparticles loaded with 5-FU by PEG-PLGA can release maintain 5 days and have inhibitory action to peritoneal dissemination of colon cancer in mice.

HMGB1 recruits myeloid derived suppressor cells to promote peritoneal dissemination of colon cancer after resection

Peritoneal metastasis of colorectal cancer is a major clinical issue and results in poor prognosis for patients after surgical resection. Here, we found that abdominal surgery trauma induced high release of high-mobility group box 1 (HMGB1) in the peritoneal cavity of mice. Recombinant HMGB1 injected in the peritoneal cavity recruited abundant myeloid derived suppressor cells (MDSCs) after the surgical trauma. HMGB1 Box-A and gemcitabine reduced the recruitment of MDSCs in the peritoneal cavity after the operation and ameliorated the peritoneal metastasis burden of colon cancer in mouse model. These results showed that abdominal surgery trauma leads to a large amount of HMGB1 released in the peritoneal cavity which recruits numerous MDSCs to promote peritoneal metastasis of colon cancer after curative surgery.

MUC2 protein expression status is useful in assessing the effects of hyperthermic intraperitoneal chemotherapy for peritoneal dissemination of colon cancer

We conducted a molecular biological investigation to determine the outcomes of hyperthermic intraperitoneal chemotherapy (HIPEC) treatment, and whether it is effective in all cases for patients with peritoneal dissemination of colon cancer. In the HIPEC group, the 3-year survival rate was 39.2%, whereas in the non-HIPEC group the 3-year survival rate was 15.6%. MUC2 expression was investigated in the HIPEC group, in patients positive for MUC2 expression, and the 3-year survival rate was 0.0%, while in patients negative for MUC2 expression, the 3-year survival rate was 61.1%. In addition, as a result of introducing MUC2-siRNA into a colon cancer cell line with high expression of the MUC2 gene, the cell death rate from heat and anticancer agents increased 40% in comparison with colon cancer cells in which scrambled siRNA had not been introduced. HIPEC therapy is thought to be effective in prolonging survival in patients with peritoneal dissemination of colon cancer, and MUC2 expression is thought to be useful as an indicator to assess its effectiveness in colon cancer cells.

Intraperitoneal radioimmunotherapy to treat the early phase of peritoneal dissemination of human colon cancer cells in a murine model

In patients with a high risk of peritoneal dissemination of colon cancer, a treatment adjuvant to surgical resection would improve their prognosis. We aimed to determine whether radioimmunotherapy employing radiolabelled monoclonal antibody would work in this situation. A murine model of peritoneal dissemination was established in female Balb/c nu/nu mice by intraperitoneal injection of LS180 human colon cancer cells. Radioimmunotherapy with 7.4 MBq of a murine IgG1, anti-colorectal A7 monoclonal antibody, radiolabelled with (131)I by the chloramine-T method was conducted intraperitoneally on days 0, 3, 7 and 14 after cell inoculation, respectively. Radioimmunotherapy at any timing improved survival of mice as compared with those of non-treated mice and mice treated with a daily dose of 30 mg x kg(-1) of 5-fluorouracil for 4 consecutive days. The best improvement was obtained when radioimmunotherapy was conducted on day 0. These results indicate that intraperitoneal radioimmunotherapy may effectively kill colon cancer cells disseminated in the peritoneal cavity before formation of tumours and, therefore, may work as an adjuvant treatment to prevent peritoneal metastasis of colon cancer.

Octreotide improved the quality of life in a child with malignant bowel obstruction caused by peritoneal dissemination of colon cancer

This is a first pediatric case about the efficacy of octreotide for improving symptoms of malignant bowel obstruction. A 12-year-old boy was referred to our hospital for treatment of transverse colon cancer with peritoneal dissemination. A transverse colectomy was undertaken with postoperative adjuvant chemotherapy. Seven months later, severe abdominal symptoms occurred caused by incomplete bowel obstruction owing to tumor progression. The patient's quality of life decreased with a resultant disturbed mental condition. His parents sought to stop chemotherapy and for him to receive palliative care at home. We suggested nasogastric tube placement, but this was rejected. After obtaining informed consent, octreotide was administered intravenously. After 1 week, abdominal symptoms improved and the boy's complaints stopped. He had a good appetite and was able to eat small amounts of food. He was able to spend his final 2 months at home without nausea and in his family surroundings.

Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo.

To study the effect of angiogenesis inhibitor TNP-470 on peritoneal dissemination of colon cancer in nude mice. The MTT assay was used to evaluate the inhibitory effect of TNP-470 on human colon cancer cell line Lovo. Lovo cells were injected into the peritoneal cavity of BABL/C nu/nu mice and the models of peritoneal dissemination were developed. Thirty nude mice were randomly divided into control and TNP-470-treated group. In TNP-470-treated group, TNP-470 was injected subcutaneously every other day from day 1 until sacrifice or death (30 mg x kg(-1)). The control group received a sham injection of the same volume saline solution. In vitro, TNP-470 inhibited the growth of Lovo cells, with its IC50 at 2.14 X 10(2) microg x L(-1). In vitro, TNP-470 demonstrated growth inhibition of tumors. Mice body weight and abdominal circumferences were significantly different between TNP-470-treated group (24.5+/-3.2 g, 7.0+/-1.1 cm) and control group (29.5+/-2.1 g, 10.3+/-1.5 cm), P=0.005 and P=0.001. The number of disseminated foci was significantly different between the control group (92.1+/-20.6) and the TNP-470-treated group (40.3+/-12.3), P<0.001. The maximal size of foci was significantly smaller in TNP-470-treated group (3.3+/-0.7 mm) than that of control (7.3+/-2.3 mm), P=0.004. Mean survival time was significantly longer in TNP-470-treated group(98.00+/-12.06 d) than that in control group (41.86+/-9.51 d), P<0.001. Angiogenesis inhibitor TNP-470 might be effective in treating peritoneal dissemination of colon cancer and improve the survival rate of nude mice.